264 research outputs found

    Multidispensor cartesian robotic printer

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    Disclosed are systems, compositions, and methods for three-dimensional (3D) printing. An example system includes a plurality dispensers configured to deposit materials from their tips and a printing surface for receiving the materials. The system includes a position sensing detector configured to detect positions of the tips of the dispensers and the location and dimensions of the printing surface. The system includes a robotic positioning device configured to drive the dispensers. The system also includes a control unit configured to receive and map in a 3D space the positions of the tips of the dispensers and the position and dimensions of the printing surface. The control unit is further configured to control the robotic positioning device to drive the dispensers relative to the printing surface in the 3D space, and to independently deposit materials on the printing surface, or on material deposited on the printing surface

    Connexin-Based Therapeutics and Tissue Engineering Approaches to the Amelioration of Chronic Pancreatitis and Type I Diabetes: Construction and Characterization of a Novel Prevascularized Bioartificial Pancreas

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    Total pancreatectomy and islet autotransplantation is a cutting-edge technique to treat chronic pancreatitis and postoperative diabetes. A major obstacle has been low islet cell survival due largely to the innate inflammatory response. Connexin43 (Cx43) channels play a key role in early inflammation and have proven to be viable therapeutic targets. Even if cell death due to early inflammation is avoided, insufficient vascularization is a primary obstacle to maintaining the viability of implanted cells. We have invented technologies targeting the inflammatory response and poor vascularization: a Cx43 mimetic peptide that inhibits inflammation and a novel prevascularized tissue engineered construct. We combined these technologies with isolated islets to create a prevascularized bioartificial pancreas that is resistant to the innate inflammatory response. Immunoconfocal microscopy showed that constructs containing islets express insulin and possess a vascular network similar to constructs without islets. Glucose stimulated islet-containing constructs displayed reduced insulin secretion compared to islets alone. However, labeling for insulin post-glucose stimulation revealed that the constructs expressed abundant levels of insulin. This discrepancy was found to be due to the expression of insulin degrading enzyme. These results suggest that the prevascularized bioartificial pancreas is potentially a tool for improving long-term islet cell survival in vivo

    Strong Coupling Constant from the Photon Structure Function

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    We extract the value of the strong coupling constant alpha_s from a single-parameter pointlike fit to the photon structure function F_2^gamma at large x and Q^2 and from a first five-parameter full (pointlike and hadronic) fit to the complete F_2^gamma data set taken at PETRA, TRISTAN, and LEP. In next-to-leading order and the MSbar renormalization and factorization schemes, we obtain alpha_s(m_Z)=0.1183 +/- 0.0050(exp.)^+0.0029_-0.0028(theor.) [pointlike] and alpha_s(m_Z)=0.1198 +/- 0.0028(exp.)^+0.0034_-0.0046(theor.) [pointlike and hadronic]. We demonstrate that the data taken at LEP have reduced the experimental error by about a factor of two, so that a competitive determination of alpha_s from F_2^gamma is now possible.Comment: 11 pages, 2 tables, 2 figures. Version accepted for publication by Phys. Rev. Let

    Population genetics of Cobia (Rachycentron canadum): implications for fishery management along the coast of the southeastern United States

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    Cobia (Rachycentron canadum) is a pelagic, migratory species with a transoceanic distribution in tropical and subtropical waters. Recreational fishing pressure on Cobia in the United States has increased substantially during the last decade, especially in areas of its annual inshore aggregations, making this species potentially susceptible to overfishing. Although Cobia along the Atlantic and Gulf coasts of the southeastern United States are currently managed as a single fishery, the genetic composition of Cobias in these areas is unclear. On the basis of a robust microsatellite data set from collections along the U.S. Atlantic coast (2008–09), offshore groups were genetically homogenous. However, the 2 sampled inshore aggregations (South Carolina and Virginia) were genetically distinct from each other, as well as from the offshore group. The recapture of stocked fish within their release estuary 2 years after release indicates that some degree of estuarine fidelity occurs within these inshore aggregations and supports the detection of their unique genetic structure at the population level. These results complement the observed high site fidelity of Cobias in South Carolina and support a recent study that confirms that Cobia spawn in the inshore aggregations. Our increased understanding of Cobia life history will be beneficial for determining the appropriate scale of fishery management for Cobia

    Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections

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    Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV

    Activated Polymorphonuclear Leukocytes Rapidly Synthesize Retinoic Acid Receptor-α: A Mechanism for Translational Control of Transcriptional Events

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    In addition to releasing preformed granular proteins, polymorphonuclear leukocytes (PMNs) synthesize chemokines and other factors under transcriptional control. Here we demonstrate that PMNs express an inducible transcriptional modulator by signal-dependent activation of specialized mechanisms that regulate messenger RNA (mRNA) translation. HL-60 myelocytic cells differentiated to surrogate PMNs respond to activation by platelet activating factor by initiating translation and with appearance of specific mRNA transcripts in polyribosomes. cDNA array analysis of the polyribosome fraction demonstrated that retinoic acid receptor (RAR)-α, a transcription factor that controls the expression of multiple genes, is one of the polyribosome-associated transcripts. Quiescent surrogate HL60 PMNs and primary human PMNs contain constitutive message for RAR-α but little or no protein. RAR-α protein is rapidly synthesized in response to platelet activating factor under the control of a specialized translational regulator, mammalian target of rapamycin, and is blocked by the therapeutic macrolide rapamycin, events consistent with features of the 5′ untranslated region of the transcript. Newly synthesized RAR-α modulates production of interleukin-8. Rapid expression of a transcription factor under translational control is a previously unrecognized mechanism in human PMNs that indicates unexpected diversity in gene regulation in this critical innate immune effector cell

    Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

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    Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires

    Simulations of Infrared Radiances Over a Deep Convective Cloud System Observed During TC4: Potential for Enhancing Nocturnal Ice Cloud Retrievals

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    Retrievals of ice cloud properties using infrared measurements at 3.7, 6.7, 7.3, 8.5, 10.8, and 12.0 microns can provide consistent results regardless of solar illumination, but are limited to cloud optical thicknesses tau 20, the 3.7 - 10.8 microns and 3.7 - 6.7 microns BTDs are the most sensitive to D(sub e). Satellite imagery appears consistent with these results. Keywords: clouds; optical depth; particle size; satellite; TC4; multispectral thermal infrare

    Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas Aeruginosa

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    Background: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). Methods: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). Results: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). Conclusions: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs
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